[Altered calcium homeostasis in chronic heart failure]

Intracellular calcium homoeostasis is greatly altered in heart failure. This does not seem to be due to altered calcium influx through L-type calcium channels but rather due to altered calcium uptake mechanisms of the sarcoplasmic reticulum. Recently, a negative force-frequency behaviour of the human myocardium has been detected in hearts from patients with severe heart failure. In the myocardium from these patients, SR-Ca(2+)-ATPase activity was decreased. The same defect has been reported in human isolated cardiac myocytes. A disturbed calcium release from the SR may also contribute to this finding of the inverse force-frequency-relationship in the failing myocardium. The altered intracellular calcium handling is connected with the diastolic and systolic failure of the myocardium. Mg++ and Na(+)-channel modulators are able to restore the positive force-frequency-relationship even in severely failing myocardium.